CoChat
Sign Up
Cited by 13

The DOI matches its Crossref record.

Requirement for p85α regulatory subunit of class IA PI3K in myeloproliferative disease driven by an activation loop mutant of KIT

Munugalavadla, Veerendra, Sims, Emily C., Chan, Rebecca J., Lenz, Stephen D., Kapur, Reuben·2008·Experimental Hematology
DOI 10.1016/j.exphem.2007.11.008
Open this paper in CoChat — free account

Abstract

Objective Oncogenic activation loop mutations of KIT are observed in acute myeloid leukemia (AML) and in myeloproliferative disorders (MPD); however, the signaling pathways that contribute to transformation via these mutations in vivo are not known. Previous studies have demonstrated hyperactivation of p85alpha regulatory subunit of class IA phosphatidylinositol-3-kinase (PI3K) in cell lines expressing the activation loop mutant of KIT (KITD816V [human] and KITD814V [murine]). Although p85alpha is hyperphosphorylated and constitutively bound to KITD814V in cell-line models; the physiologic significance of this biochemical phenomenon in KITD814V-induced transformation is not known. Materials and methods Here, we describe the generation of a new mouse model to study KITD814V-induced transformation in myeloid cells as opposed to previously described models that primarily result in the generation of disease resembling acute lymphocytic leukemia. Results Our results show that transplantation of KITD814V expressing bone marrow cells from C57/BL6 strain of mice into syngeneic recipients results in a fatal MPD. Importantly, in this model, transplantation of KITD814V expressing p85alpha-deficient bone marrow cells rescues the MPD phenotype. Conclusions Our results describe the generation of a new murine transplant model to study KITD814V-induced transformation and identify p85alpha as potential therapeutic target for the treatment of KITD814V-bearing diseases.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.exphem.2007.11.008

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 31

  1. Hirota, 1998, Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors, Science, 279, 577, 10.1126/science.279.5350.577 · DOI
  2. Longley, 1996, Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm, Nat Genet, 12, 312, 10.1038/ng0396-312 · DOI
  3. Beghini, 2000, C-kit mutations in core binding factor leukemias, Blood, 95, 726, 10.1182/blood.V95.2.726 · DOI
  4. Tian, 1999, Activating c-kit gene mutations in human germ cell tumors, Am J Pathol, 154, 1643, 10.1016/S0002-9440(10)65419-3 · DOI
  5. Nagata, 1995, Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder, Proc Natl Acad Sci U S A, 92, 10560, 10.1073/pnas.92.23.10560 · DOI
  6. Feger, 2002, Kit and c-kit mutations in mastocytosis: a short overview with special reference to novel molecular and diagnostic concepts, Int Arch Allergy Immunol, 127, 110, 10.1159/000048179 · DOI
  7. Care, 2003, Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias, Br J Haematol, 121, 775, 10.1046/j.1365-2141.2003.04362.x · DOI
  8. Nanri, 2005, Imatinib mesylate for refractory acute myeloblastic leukemia harboring inv(16) and a C-KIT exon 8 mutation, Leukemia, 19, 1673, 10.1038/sj.leu.2403889 · DOI
  9. Schnittger, 2006, KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival, Blood, 107, 1791, 10.1182/blood-2005-04-1466 · DOI
  10. Cairoli, 2006, Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study, Blood, 107, 3463, 10.1182/blood-2005-09-3640 · DOI
  11. Shimada, 2006, KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group, Blood, 107, 1806, 10.1182/blood-2005-08-3408 · DOI
  12. Akin, 2003, Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit, Exp Hematol, 31, 686, 10.1016/S0301-472X(03)00112-7 · DOI
  13. Pardanani, 2003, Imatinib for systemic mast-cell disease, Lancet, 362, 535, 10.1016/S0140-6736(03)14115-3 · DOI
  14. Ma, 2002, The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations, Blood, 99, 1741, 10.1182/blood.V99.5.1741 · DOI
  15. Piao, 1996, Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1, Proc Natl Acad Sci U S A, 93, 14665, 10.1073/pnas.93.25.14665 · DOI
  16. Ning, 2001, Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells, Blood, 97, 3559, 10.1182/blood.V97.11.3559 · DOI
  17. Ning, 2001, STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity, Oncogene, 20, 4528, 10.1038/sj.onc.1204590 · DOI
  18. Chian, 2001, Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant, Blood, 98, 1365, 10.1182/blood.V98.5.1365 · DOI
  19. Shivakrupa, 2003, Phosphatidylinositol 3 kinase is required for growth of mast cells expressing the kit catalytic domain mutant, Cancer Res, 63, 4412
  20. Hashimoto, 2003, Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the Asp814Val mutation, Blood, 101, 1094, 10.1182/blood-2002-01-0177 · DOI
  21. Kosmider, 2005, Kit-activating mutations cooperate with Spi-1/PU.1 overexpression to promote tumorigenic progression during erythroleukemia in mice, Cancer Cell, 8, 467, 10.1016/j.ccr.2005.11.009 · DOI · Paper page
  22. Wymann, 2003, Phosphoinositide 3-kinase signalling—which way to target?, Trends Pharmacol Sci, 24, 366, 10.1016/S0165-6147(03)00163-9 · DOI
  23. Geering, 2007, Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers, Proc Natl Acad Sci U S A, 104, 7809, 10.1073/pnas.0700373104 · DOI
  24. Samuels, 2004, High frequency of mutations of the PIK3CA gene in human cancers, Science, 304, 554, 10.1126/science.1096502 · DOI
  25. Bader, 2005, Oncogenic PI3K deregulates transcription and translation, Nat Rev Cancer, 5, 921, 10.1038/nrc1753 · DOI
  26. Terauchi, 1999, Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase, Nat Genet, 21, 230, 10.1038/6023 · DOI · Paper page
  27. Williams, 2000, Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency, Blood, 96, 1646
  28. Munugalavadla, 2007, Genetic and pharmacologic evidence implicating the p85{α}, but not p85{β}, regulatory subunit of PI3K and Rac2 GTPase in regulating oncogenic KIT-induced transformation in acute myeloid leukemia and systemic mastocytosis, Blood, 110, 1612, 10.1182/blood-2006-10-053058 · DOI
  29. Kitayama, 1996, Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase, Blood, 88, 995, 10.1182/blood.V88.3.995.995 · DOI
  30. Xiang, 2007, Neoplasia driven by mutant c-KIT is mediated by intracellular, not plasma membrane, receptor signaling, Mol Cell Biol, 27, 267, 10.1128/MCB.01153-06 · DOI
  31. Niv, 2004, Sequence-based design of kinase inhibitors applicable for therapeutics and target identification, J Biol Chem, 279, 1242, 10.1074/jbc.M306723200 · DOI

Cited by

See all 13

Metadata

Authors
Munugalavadla, V., Sims, E. C., Chan, R. J., Lenz, S. D., & Kapur, R.
Venue
Experimental Hematology
Publisher
Elsevier BV
Published
2008-03
Volume
36
Issue
3
Pages
301-308
ISSN
0301-472X
DOI
10.1016/j.exphem.2007.11.008
Cited by
13
References
0
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Requirement for p85α regulatory subunit of class IA PI3K in myeloproliferative disease driven by an activation loop mutant of KIT. https://app.cochat.ai/papers/10.1016/j.exphem.2007.11.008
The paper
Munugalavadla, V., Sims, E. C., Chan, R. J., Lenz, S. D., & Kapur, R. (2008). Requirement for p85α regulatory subunit of class IA PI3K in myeloproliferative disease driven by an activation loop mutant of KIT. Experimental Hematology. https://doi.org/10.1016/j.exphem.2007.11.008